This is an application for an NINDS Exploratory / Developmental Grant (R21), entitled "Decreased Motor Thresholds in Dystonia." The goal of this project is to begin comparing the relative contributions of the motor and somatosensory systems to dystonic pathology by measuring brain activity in focal hand dystonic patients during motor and somatosensory tasks, working toward a hypothesis that the motor system plays a more primary role than the somatosensory system in dystonia. Specifically, we will make precise anatomical distinctions between motor and somatosensory cortical regions in our analysis of brain activity measured in dystonic patients during simple finger-tapping and finger-stimulation tasks (Aim 1). We will also use perfusion MRI and hemodynamic response timecourses to address some basic questions about "resting" activity in focal hand dystonic patients, both to guide our experimental design, and to potentially demonstrate how motor task repetition may lead to increased resting activity in dystonia (Aim 2). Finally, we will begin to develop tasks that engage the motor and somatosensory systems near activity threshold, with an overall aim of finding new ways of detecting patient/control differences in motor and somatosensory activity, and with a specific hypothesis that motor activity thresholds may be decreased in focal hand dystonia (Aim 3). In the future, we will use these tools to assess how botulinum toxin and other treatments of the disorder influence brain motor and somatosensory abnormalities, both in the short- and long-term. The proposed studies are expected to generate novel insights into neural mechanisms of dystonia, and eventually lead to significant improvements in the treatment of this debilitating disorder. The motor/somatosensory comparisons and "resting" activity measurements will allow us to gain new information about the relative roles of motor and sensory systems in dystonia, and increase the precision and accuracy of information gained from this and future brain imaging studies of this disorder. The "motor threshold" tasks are expected to provide evidence for decreased motor thresholds in dystonia that extend beyond primary motor cortex. Understanding the relative roles of motor and somatosensory systems in dystonic pathology will be a crucial step in determining which of the existing treatments for the disorder are most successful, and will allow us to better target new treatments. [unreadable] [unreadable]